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Given the vast occurrence and availability of both primary amides and phenols, the synthesis of N-aryl amides via direct coupling between these starting materials would be much attractive. Herein, we report an efficient method for the mechanochemical synthesis of N-aryl amides via ruthenium-catalyzed direct amidation of unprotected phenols with primary amides with water as the sole byproduct. Unexpectedly, replacing amides with methyl carboxylic acids, esters, or ketones, the same reaction led to the formation of α-aryl carbonyl derivatives instead of the anticipated aryl carboxylates. The synthetic strategy accepts a wide scope of primary amides, alkyl carbonyls, and phenolic substrates to deliver 28 expected N-aryl amides and 14 unexpected α-aryl carbonyl derivatives with good to excellent yields. The developed synthetic approach would serve as the better alternative to the classical cross-coupling reactions in context to the PASE (pot, atom, and step economy) synthesis and late-stage modification of structurally complex molecules, including natural products and pharmaceuticals.
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http://dx.doi.org/10.1002/chem.202500862 | DOI Listing |
ChemMedChem
September 2025
Departamento de Química Orgánica, Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, 04510, México.
We describe the synthesis and activity against methicillin-resistant Staphylococcus aureus (MRSA) of a collection of urea-containing amides. The approach considered the ureido group as a bioisoster of known FabI inhibitors. NMR characterization and density functional theory studies demonstrated the presence of s-cis and s-trans rotamers in the N-benzyl examples (series 2).
View Article and Find Full Text PDFChem Asian J
August 2025
Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, Botanic Garden, Howrah, West Bengal, 711103, India.
We report, for the first time, an efficient manganese (Mn)-assisted copper (Cu)-catalyzed cross-coupling reaction that involves a range of aryl, heteroaryl, and styrenyl halides with various primary amides, sulfonamides, and cinnamamide, in air without solvents or added ligands. This cost-effective protocol successfully produced the desired cross-coupling products-N-aryl and N-styryl amides, sulfonamides, and cinnamamides-in good to excellent yields. It demonstrates a broad substrate scope (98 examples) and is tolerant to various sensitive functionalities such as -COCH, -COEt, -NO, -OH, -NH, -Br, -Cl, -F, -CF, -OCF, -OCH, -CHPh, and heterocycles.
View Article and Find Full Text PDFChem Commun (Camb)
August 2025
College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, China.
Hetero-atom migration strategy is a powerful tool to access complex molecules. Herein, we disclose a cascade radical 1,2--migration/ring-opening of -aryl bicyclobutyl amides (BCBs) with β-bromo α-amino acid esters by cooperative Ni/diboron catalysis, which afforded a wide array of spirocyclobutyl oxindoles tethering a β-amino acid motif under room temperature conditions. The method suppressed the typical intramolecular C(sp)-H cyclization of β-bromo amino acid esters after 1,2--migration, successfully incorporating β-amino acid moieties into the spirocyclobutyl oxindole scaffolds.
View Article and Find Full Text PDFOrg Lett
July 2025
Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China.
A visible-light-promoted thiolate-catalyzed sequential carboxylation/arylation of -aryl acrylamides with CO has been accomplished, leading to a range of functionalized oxindole-3-acetic acids with good efficiency. Mechanism studies indicated that the EDA complex derived from thiolate and alkene would be a key intermediate in this reaction. Unexpectedly, switching to -aryl propargyl amides led to a base-promoted intermolecular nucleophilic thio/carboxylation of the alkyne with CO, affording various thioacrylic acids in good yields under visible-light-free conditions.
View Article and Find Full Text PDFChemistry
August 2025
School of Chemistry, Purdie Building, North Haugh, University of St Andrews, St Andrews, KY16 9ST, UK.
An in-depth computational probe of the hydroaminoalkylation of 1,3-dienes with N-aryl substituted amines by a tethered bis(ureate)-ligated zirconium compound is reported. The mechanistic proposal derived from smooth energy profiles acquired by employing a reliable computational protocol complies with previous experimental mechanistic studies, providing a more advanced understanding of intricate mechanistic aspects. The high degree of regioselectivity achieved for reversible diene insertion and butenyl tether protonolysis is instrumental for the generation of the main product, (E)-4,1 linear homoallylic amine.
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